AAPS J. 2022 Jul 6;24(4):79.doi: 10.1208/s12248-022-00730-0.

Ruo-Jing Li ¹, Lian Ma ², Hyewon Kim ², Insook Kim ², Lesley Hanes ³, Tara Altepeter ³, Jessica Lee ³, Jiang Liu ², Hao Zhu ², Yaning Wang ⁴

Author information

¹Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA. Ruojing.Li@fda.hhs.gov.

²Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.

³Division of Gastroenterology, Office of Immunology and Inflammation, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

⁴Createrna Science and Technology, Wuhan, China.

Abstract

On February 24, 2021, the U.S. Food and Drug Administration (FDA) approved an efficacy supplement for HUMIRA® (adalimumab) injection to expand the indication of treatment of moderately to severely active ulcerative colitis (UC) to include pediatric patients 5 years of age and older. The effectiveness in pediatric patients with moderately to severely active UC was studied in a multicenter, randomized, double-blind trial (Study PUC-I, NCT02065557) in 93 pediatric patients 5 to 17 years of age. Adalimumab has been widely studied in multiple indications in adult and pediatric populations with a well-established safety profile; no apparent exposure-safety relationship has been identified in various pediatric populations treated with adalimumab across multiple indications. The approved dosing regimen in pediatric patients with UC differs from the regimen studied in the clinical trial and was determined based on a model-informed exposure bridging strategy, incorporating both efficacy and safety considerations. Specifically, the differences included switches from body weight-based (mg/kg) dosing regimens used in the pediatric trial to body weight-tiered, fixed-dose regimens, changes in dosing schedule, and the addition of an option of a less frequent dosing regimen for maintenance that was not studied in the clinical trial. This article provides a case example of successful model-informed drug development (MIDD), where modeling and simulation were utilized in combination with observed data from a clinical trial of limited size and scope to ultimately support the adalimumab approval in pediatric patients with UC.